Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study
Por:
Hernández-Sánchez, A, González, T, Sobas, M, Sträng, E, Castellani, G, Abáigar, M, Valk, PJM, Ramiro, AV, Benner, A, Metzeler, KH, Azibeiro, R, Tettero, JM, Martínez-López, J, Pratcorona, M, Elicegui, JM, Mills, KI, Thiede, C, Sanz, G, Döhner, K, Heuser, M, Haferlach, T, Turki, AT, Reinhardt, D, Schulze-Rath, R, Barbus, M, Hernández-Rivas, JM, Huntly, B, Ossenkoppele, G, Döhner, H, Bullinger, L
Publicada:
4 jul 2024
Ahead of Print:
1 jul 2024
Resumen:
Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.
Filiaciones:
Hernández-Sánchez, A:
Univ Hosp Salamanca, Hematol Dept, Salamanca, Spain
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
USAL CSIC, Canc Res Ctr Salamanca IBMCC, Salamanca, Spain
González, T:
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
USAL CSIC, Canc Res Ctr Salamanca IBMCC, Salamanca, Spain
Sobas, M:
Wroclaw Med Univ, Wroclaw, Poland
Sträng, E:
Charite Univ Med Berlin, Berlin, Germany
Castellani, G:
Univ Bologna, DIMES, Bologna, Italy
Abáigar, M:
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
USAL CSIC, Canc Res Ctr Salamanca IBMCC, Salamanca, Spain
Valk, PJM:
Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Hematol, Rotterdam, Netherlands
Ramiro, AV:
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
USAL CSIC, Canc Res Ctr Salamanca IBMCC, Salamanca, Spain
Benner, A:
German Canc Res Ctr, Div Biostat, Heidelberg, Germany
Metzeler, KH:
Univ Leipzig, Leipzig, Germany
Azibeiro, R:
Univ Hosp Salamanca, Hematol Dept, Salamanca, Spain
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
Tettero, JM:
Amsterdam UMC Locat VUMC, Dept Hematol, Amsterdam, Netherlands
Martínez-López, J:
Hosp Univ 12 Octubre, Madrid, Spain
Pratcorona, M:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain
Elicegui, JM:
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
USAL CSIC, Canc Res Ctr Salamanca IBMCC, Salamanca, Spain
Mills, KI:
Queens Univ, Patrick G Johnston Ctr Canc Res, Belfast, North Ireland
Thiede, C:
Univ Tech Dresden, Med Dept, Dresden, Germany
Sanz, G:
Inst Salud Carlos III, CIBERONC, Madrid, Spain
Hosp Univ & Politecn La Fe, Valencia, Spain
Döhner, K:
Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany
Heuser, M:
Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpla, Hannover, Germany
Haferlach, T:
MLL Munich Leukemia Lab, Munich, Germany
Turki, AT:
Ruhr Univ Bochum, Marienhosp Univ Hosp, Bochum, Germany
Univ Klinikum Essen, Essen, Germany
Reinhardt, D:
Univ Duisburg Essen, Univ Hosp Essen, Dept Pediat 3, Essen, Germany
Schulze-Rath, R:
Bayer AG, Pharmaceut Div, Berlin, Germany
Barbus, M:
AbbVie Deutschland GmbH & Co KG, Wiesbaden, Germany
Hernández-Rivas, JM:
Univ Hosp Salamanca, Hematol Dept, Salamanca, Spain
Inst Biomed Res Salamanca IBSAL, Salamanca, Spain
USAL CSIC, Canc Res Ctr Salamanca IBMCC, Salamanca, Spain
Univ Salamanca, Dept Med, Salamanca, Spain
Huntly, B:
Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England
Ossenkoppele, G:
Amsterdam UMC Locat VUMC, Dept Hematol, Amsterdam, Netherlands
Döhner, H:
Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany
Bullinger, L:
Charite Univ Med Berlin, Dept Hematol Oncol & Canc Immunol, Berlin, Germany
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